age-related declines in fitness. The accumulation of random, germline age-related mutated alleles is known as mutation accumulation. Note that somatic mutations are not heritable, they are only a source of developmental variation. Studies done on Drosophila melanogaster have shown that mutation accumulation drives the combination of alleles which have "age-specific additive effects" that cause a decline in stress response and ultimately an age-related decline in fitness. The number of germ cell divisions per generation is variable among lineages, and relates to genome size; for humans; 401 germ cell divisions occur per generation in males and 31 in females. Mutation accumulation Germ line The first modern theory of mammal ageing was formulated by Peter Medawar in 1952. This theory formed in the previous decade with J. B. S. Haldane and his selection shadow concept. The development of human civilization has shifted the selective shadow as the conditions that humans now live in include improved quality of victuals, living conditions, and healthcare. This improved healthcare includes modern medicine such as antibiotics and new medical technology. A few studies in Drosophila have shown that the age of expression of novel deleterious mutations, defines the effects they contribute on mortality. Overall, however; although their frequency increases, their effects and variation decreases with age. There is no theory that explains how these deleterious mutations affect fitness on different ages and the evolution of senescence. Their idea was that ageing was a matter of neglect, as nature is a highly competitive place. Almost all animals die in the wild from predators, disease, or accidents, which lowers the average age of death. Therefore, there is not much reason why the body should remain fit for the long haul because selection pressure is low for traits that would maintain viability past the time when most animals would have died anyway. Metabolic diseases come along due to the low demand for physical activity in modern civilization compared to times where humans had to forage in the wild for survival. With the selective shadow now shifted, humans must deal with these new selective pressures. Senescence is considered a by-product of physiology because our cell metabolism creates products that are toxic, we get mutations when we age, and we don't have enough stem cells that regenerate. Why did selection not find and favor mutations in ways that allow us, for example, to regenerate our cells, or to not produce toxic metabolism?